HLA-II-Associated HIV-1 Adaptation Decreases CD4
            <sup>+</sup>
            T-Cell Responses in HIV-1 Vaccine Recipients

Files, Jacob K.; Henostroza, Sebastian; Fucile, Christopher; Maroney, Kevin; Fram, Tim; Mallal, S.; Kalams, Spyros A.; Carlson, Jonathan M.; Rosenberg, Alexander F.; Erdmann, Nathan; Bansal, Anju

doi:10.1128/jvi.01191-22

J Virol

2022

DOI: 10.1128/jvi.01191-22

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HLA-II-Associated HIV-1 Adaptation Decreases CD4 ⁺ T-Cell Responses in HIV-1 Vaccine Recipients

Jacob K. Files

Sebastian Henostroza

Christopher Fucile

et al.

Abstract: Despite decades of research, an effective HIV-1 vaccine remains elusive. Vaccine strategies leading to the generation of broadly neutralizing antibodies are likely needed to provide the best opportunity of generating a protective immune response against HIV-1.

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2024

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Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119

Kalams,

Felber,

Mullins

et al. 2024

JCI Insight

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BACKGROUND An HIV-1 DNA vaccine composed of 7 highly conserved, structurally important elements (conserved elements, CE) of p24 Gag was tested in a phase I randomized, double-blind clinical trial (HVTN 119, NCT03181789) in people without HIV. DNA vaccination of CE prime/CE+p55 Gag boost was compared with p55 Gag . METHODS Two groups ( n = 25) received 4 DNA vaccinations (CE/CE+p55 Gag or p55 Gag ) by intramuscular injection/electroporation, including IL-12 DNA adjuvant. The placebo group ( n = 6) received saline. Participants were followed for safety and tolerability. Immunogenicity was assessed for T cell and antibody responses. RESULTS Both regimens were safe and generally well tolerated. The p24CE vaccine was immunogenic and significantly boosted by CE+p55 Gag (64% CD4 + , P = 0.037; 42% CD8 + , P = 0.004). CE+p55 Gag induced responses to 5 of 7 CE, compared with only 2 CE by p55 Gag DNA, with a higher response to CE5 in 30% of individuals ( P = 0.006). CE+p55 Gag induced significantly higher CD4 + CE T cell breadth (0.68 vs. 0.22 CE; P = 0.029) and a strong trend for overall T cell breadth (1.14 vs. 0.52 CE; P = 0.051). Both groups developed high cellular and humoral responses. p24CE vaccine–induced CD4 + CE T cell responses correlated ( P = 0.007) with p24 Gag antibody responses. CONCLUSION The CE/CE+p55 Gag DNA vaccine induced T cell responses to conserved regions in p24 Gag , increasing breadth and epitope recognition throughout p55 Gag compared with p55 Gag DNA. Vaccines focusing immune responses by priming responses to highly conserved regions could be part of a comprehensive HIV vaccine strategy. TRIAL REGISTRATION Clinical Trials.gov NCT03181789 FUNDING HVTN, NIAID/NIH

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Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119

Kalams,

Felber,

Mullins

et al. 2024

JCI Insight

View full text Add to dashboard Cite

show abstract

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HLA-II-Associated HIV-1 Adaptation Decreases CD4 ⁺ T-Cell Responses in HIV-1 Vaccine Recipients

Abstract: Despite decades of research, an effective HIV-1 vaccine remains elusive. Vaccine strategies leading to the generation of broadly neutralizing antibodies are likely needed to provide the best opportunity of generating a protective immune response against HIV-1.

Cited by 1 publication

References 45 publications

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119

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HLA-II-Associated HIV-1 Adaptation Decreases CD4 + T-Cell Responses in HIV-1 Vaccine Recipients

Abstract: Despite decades of research, an effective HIV-1 vaccine remains elusive. Vaccine strategies leading to the generation of broadly neutralizing antibodies are likely needed to provide the best opportunity of generating a protective immune response against HIV-1.

Cited by 1 publication

References 45 publications

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119

Focusing HIV-1 Gag T cell responses to highly conserved regions by DNA vaccination in HVTN 119

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HLA-II-Associated HIV-1 Adaptation Decreases CD4 ⁺ T-Cell Responses in HIV-1 Vaccine Recipients